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Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

Roch Houot 1, 2 Tony Marchand 2, 1 Nathalie Dhédin 3 Willy Lescaut 4 Anne Thiebaut-Bertrand 5 Sylvie Francois 6 Aspasia Stamatoullas-Bastard 7 Pierre-Simon Rohrlich 8 Hélène Labussière Wallet 9 Luca Castagna 10, 11 Armando Santoro 12 Veronika Bachanova 13 Scott C. Bresler 14 Amitabh Srivastava 14 Harim Kim 15 Emily Pesek 14 Marie Chammas 14 Carol Reynolds 14 Vincent T. Ho 14 Joseph H. Antin 14 Jerome Ritz 14 Robert J. Soiffer 14 Philippe Armand 14 Reid W. Merryman 16 Haesook T. Kim 16 Pier Luigi Zinzani 17 Carmelo Carlo-Stella 18 Stephen M. Ansell 19 Miguel-Angel Perales 20 Abraham Avigdor 21 Ahmad S. Halwani 22
Abstract : Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1(+) T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade.
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Submitted on : Tuesday, May 2, 2017 - 3:57:22 PM
Last modification on : Wednesday, August 19, 2020 - 11:17:24 AM

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Roch Houot, Tony Marchand, Nathalie Dhédin, Willy Lescaut, Anne Thiebaut-Bertrand, et al.. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood, American Society of Hematology, 2017, 129 (10), pp.1380-1388. ⟨10.1182/blood-2016-09-738385⟩. ⟨hal-01517054⟩

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